Project Summary/Abstract Rationale: Clostridium difficile (C. difficile) infection disproportionally affects the elderly population with a predominance of patients affected being from long-term care facilities (LTCFs). Upwards of 40 to 50% of CDI cases are now from LTCFs and colonization rates remain high within these facilities, with as many as half of the residents being colonized with C. difficile at any given time. Carriage of C. difficile is a well documented source of new CDI cases, however approaches to managing carriage as a means to prevent CDI are lacking. One factor that has become of increasing contemporary interest and a target of preventive strategies is the human microbiome. Seeing how elderly residents in long-term care gain a defined population of bacteria that are associated with increased frailty and lead to an increased risk of disease, we need a better understanding of the microbiome factors that change as an elder moves into long-term care in order to lay the foundation for targeted interventions to prevent the spread of CDI. Candidate: As an Assistant Professor of Emergency Medicine at the University of Massachusetts Medical School, the PI has published original investigations describing the dysbiotic patterns seen within the intestines of nursing home elders and how different medications are associated with an increased risk of CDI. The PI's short-term goals are to gain advanced training in geriatric medicine and the microbiome sciences. This training program and proposed research project will facilitate the PI's development as an independent, federally-funded, aging researcher whose career will be focused on preventing healthcare-associated diseases in nursing home elderly populations. Research: We hypothesize that significant shifts in the metagenomic profiles of the older patient's gut microbiome occur after admission to an LTCF that place them at increased risk for C. difficile. This hypothesis will be addressed in the following Specific Aims: (1) to characterize the metagenomic changes that occur in the intestinal microbiome of elderly resident newly admitted to an LTCF; (2) to characterize the metagenomic changes that occur in LTCF residents to identify which factors are associated with a resident becoming a C. difficile carrier; and (3) to compare the microbiome changes in patients transitioning to LTCF care to their roommates microbiome profile. This proposal has the potential to impact the growing public health problem of CDI in elderly LTCF residents through future R01 funded investigations focusing on novel techniques to predict and prevent C. difficile carriage and CDI in the LTCF elderly population.